Antrodia camphorata, a medicinal fungus, is used as tonic in Taiwan folk medicine with antidotes function. It plays an important role in treatment of alcohol and drug intoxication and itchy skin and also has anti-tumor efficacy. Antrocin is isolated from methanol extract of Antrodia camphorata and characterized by X-ray diffraction for the three-dimensional structure of sesquiterpene lactones compound (Chiang, H. C., Wu, D. P., Cherng, I. W., Ueng, C. H. Phytochem. 1995, 39, 613-616). Recently, antrocin is proved to be a potent antagonist of a variety of cancers, against MDA-MB-231 cells of metastatic breast cancer with an IC50 value of 0.6 μM, as well as dual inhibitor of Akt/mTOR (Rao, Y. K., Wu, A. T. H., Geethangili, M., Huang, M. T., Chao, W. J., Wu, C. H., Deng, W. P., Yeh, C. T., Tzeng, Y. M. Chem. Res. Toxicol. 2011, 24, 238-245). Thus, it arouses high interest. Among the identified compounds isolated and purified from Antrodia camphorate, antrocin with small molecular weight (MW=234) has special bioactivity and potential to be developed into clinical trials reagents for treating metastatic breast cancer. The needs for antrocin in biomedical community are of considerable importance, but there are many issues to be resolve due to current technique. In terms of quantity and method, antrocin obtained from nature have certain limitations. Only synthetic method is sufficient to meet the vast needs of the market. There are no literature reports the same process to synthesize racemic antrocin, and no one uses the same synthetic process to synthesize optically active antrocin.
In previous synthetic technique, there have been related literature reported (Dailey, 0. D. Jr., Fuchs, P. L., J. Org. Chem. 1980, 45, 216-236; Armour, A. G., Buchi, G., Eschenmoser, A., Storni, A., Helv. Chim. Acta., 1959, 42, 2233.), as shown in FIG. 1. The trans-compound (±)-7 could be prepared appropriately through pathway of racemic compound (±)-6 formed from 4-methoxy-phenylaceitic acid and cyanide addition reaction.
Although using such synthesis techniques can roughly synthesize the needed racemic structure of trans-decalone, the follow-up process requires tedious modification and some special and expensive reagents to have a chance to achieve the synthesis of racemic antrocin. However, under these stringent conditions, the synthesis still generates more racemic byproduct remained. It will increase the process of separation and purification, and also has great risk behind, comprising some possible toxic substances in the end product. Therefore, the greatest challenge lies in chiral synthesis of optical isomers. It is necessary to perform optical resolution first, resulting in an optically active intermediate, thereby synthesizing antrocin compound in a straightforward manner to perform the process, in order to reduce the price of the product and enhance its purity and practicality.